Test cartridge with integrated transfer module

ABSTRACT

A system that includes a cartridge housing and a hollow transfer module, according to an embodiment is described herein. The cartridge housing further includes at least one sample inlet, a plurality of storage chambers, a plurality of reaction chambers, and a fluidic network. The fluidic network is designed to connect the at least one sample inlet, a portion of the plurality of storage chambers and the portion of the plurality of reaction chambers to a first plurality of ports located on an inner surface of the cartridge housing. The hollow transfer module includes a second plurality of ports along an outer surface of the transfer module that lead to a central chamber within the transfer module. The transfer module is designed to move laterally within the cartridge housing. The lateral movement of the transfer module aligns at least a portion of the first plurality of ports with at least a portion of the second plurality of ports.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No. 14/743,227filed on Jun. 18, 2015, which is a divisional of U.S. application Ser.No. 13/836,845 filed on Mar. 15, 2013 (now U.S. Pat. No. 9,062,342),which claims the benefit under 35 U.S.C. § 119(e), to provisionalapplication No. 61/611,784 filed on Mar. 16, 2012, the disclosures ofwhich are each incorporated by reference herein in their entirety.

BACKGROUND

Field

Embodiments of the present invention relate to the field of clinicaldiagnostic tools.

Background

Given the complexity of the automation of molecular testing andimmunoassay techniques, there is a lack of products that provideadequate performances to be clinically usable in near patient testingsettings. Typical molecular testing includes various processes involvingthe correct dosage of reagents, sample introduction, lysis of cells toextract DNA or RNA, purification steps, and amplification for itssubsequent detection. Even though there are central laboratory roboticplatforms that automate these processes, for many tests requiring ashort turnaround time, the central laboratory cannot provide the resultsin the needed time requirements.

However, it is difficult to implement systems in a clinical setting thatprovide accurate, trustworthy results at a reasonable expense. Given thecomplicated nature of various molecular testing techniques, the resultsare prone to error if the testing parameters are not carefullycontrolled or if the environmental conditions are not ideal. Forexample, existing instrumentation for PCR techniques has experiencedhigh entry barriers for clinical diagnosis applications due to thebackground generated by exogenous sources of DNA. In the case ofspecific tests of pathogens, the predominant source of contamination isa result of previous reactions carried out in pipettes, tubes, orgeneral laboratory equipment. Additionally, the use of moleculartechniques for detection of microbial pathogens can produce falsenegatives. The false negatives may result from, for example: improperdisposal of agents that inhibit the Polymerase Chain Reaction (PCR) suchas hemoglobin, urine or sputum; inefficient release of DNA from cells;or low efficiency in extraction and purification of DNA or RNA.

The fact that molecular techniques have exceptional sensitivity levelsat concentrations lower than the previous reference methods makes itrather difficult to obtain clinically relevant conclusions, whileavoiding erroneous calls with false positives. To minimize this problem,especially for the detection of pathogen microorganisms, the tests musthave quantification capability. It has therefore become increasinglynecessary to perform multiplexed assays and arrays of tests toconsolidate enough data to make confident conclusions. As an example,one of the main limitations of existing PCR-based tests is the inabilityto perform amplifications of different target genes simultaneously.While techniques such as microarrays provide very high multiplexingcapacity, their main limitation is the low speed in obtaining theresults, which often have no positive impact on patient management.

BRIEF SUMMARY

A clinical diagnostic platform can integrate a variety of analyticaltesting processes to reduce errors, costs and testing time.

In an embodiment, a system includes a cartridge housing and a hollowtransfer module. The cartridge housing further includes at least onesample inlet, a plurality of storage chambers, a plurality of reactionchambers, and a fluidic network. The fluidic network is designed toconnect the at least one sample inlet, a portion of the plurality ofstorage chambers and the portion of the plurality of reaction chambersto a first plurality of ports located on an inner surface of thecartridge housing. The hollow transfer module includes a secondplurality of ports along an outer surface of the transfer module thatlead to a central chamber within the transfer module. The transfermodule is designed to move laterally within the cartridge housing. Thelateral movement of the transfer module aligns at least a portion of thefirst plurality of ports with at least a portion of the second pluralityof ports.

In an embodiment, a transfer module includes an inner housing enclosinga central chamber and a jacket formed around the inner housing. Thejacket includes patterned ridges along the outer surface of the jacket.The patterned ridges are designed to create a plurality of valve regionsalong the outer surface of the jacket when the transfer module is placedwithin an enclosure that comes into contact with the patterned ridges.The jacket further includes a plurality of ports extending through thejacket and the inner housing into the central chamber. The plurality ofports are located within one or more of the plurality of valve regionscreated by the patterned ridges. One of the plurality of valve regionswith a corresponding port extending into the central chamber is designedto be pressurized separately from other regions in the plurality ofvalve regions, such that the pressurization generates a fluid floweither into or out of the central chamber via one or more of theplurality of ports.

An example method is described. The method includes laterallytranslating a transfer module to align a first port of the transfermodule having a central chamber to a port of the first chamber. Themethod further includes drawing a sample into the central chamber fromthe first chamber via a first pressure differential. Once the sample isin the central chamber, the method includes laterally translating thetransfer module to align a second port of the transfer module to a portof a second chamber and drawing the sample into the second chamber fromthe central chamber via a second pressure differential.

Another example method is described. The method includes laterallytranslating a transfer module within a housing to align a structure onan outer surface of the transfer module with a first port associatedwith a first chamber and with a second port associated with a secondchamber. The method further includes drawing a sample from the firstchamber to the second chamber via at least the structure aligned overthe first port and the second port. The method continues with drawingthe sample from the second chamber to a third chamber located within thetransfer module via a port through a wall of the transfer module.

BRIEF DESCRIPTION OF THE DRAWINGS/FIGURES

The accompanying drawings, which are incorporated herein and form a partof the specification, illustrate embodiments of the present inventionand, together with the description, further serve to explain theprinciples of the invention and to enable a person skilled in thepertinent art to make and use the invention.

FIG. 1 displays a graphical representation of the test cartridge system,according to an embodiment.

FIGS. 2A-2D display various views of a test cartridge system, accordingto an embodiment.

FIGS. 3A-3D display various views of the inner housing of a transfermodule, according to an embodiment.

FIGS. 4A-4C display three views of a jacket of the transfer module,according to an embodiment.

FIGS. 5A and 5B display graphical representations of a test cartridgesystem, according to an embodiment.

FIGS. 6A and 6B display various views of a test cartridge system,according to an embodiment.

FIGS. 7A-7F display various views of a transfer module, according to anembodiment.

FIGS. 8A and 8B display swabs within a test cartridge system, accordingto some embodiments.

FIG. 9 is a diagram illustrating a method performed by a test cartridgesystem, according to an embodiment.

FIG. 10 is a diagram illustrating a method performed by a test cartridgesystem, according to an embodiment.

Embodiments of the present invention will be described with reference tothe accompanying drawings.

DETAILED DESCRIPTION

Although specific configurations and arrangements are discussed, itshould be understood that this is done for illustrative purposes only. Aperson skilled in the pertinent art will recognize that otherconfigurations and arrangements can be used without departing from thespirit and scope of the present invention. It will be apparent to aperson skilled in the pertinent art that this invention can also beemployed in a variety of other applications.

It is noted that references in the specification to “one embodiment,”“an embodiment,” “an example embodiment,” etc., indicate that theembodiment described may include a particular feature, structure, orcharacteristic, but every embodiment may not necessarily include theparticular feature, structure, or characteristic. Moreover, such phrasesdo not necessarily refer to the same embodiment. Further, when aparticular feature, structure or characteristic is described inconnection with an embodiment, it would be within the knowledge of oneskilled in the art to effect such feature, structure or characteristicin connection with other embodiments whether or not explicitlydescribed.

Embodiments described herein relate to a test cartridge system forperforming a variety of molecular, immunoassay, or biochemical tests,etc. In an embodiment, the test cartridge integrates all of thecomponents necessary to perform such tests into a single, disposablepackage. The test cartridge may be configured to be analyzed by anexternal measurement system which provides data related to the reactionsthat take place within the test cartridge.

In one example, a single test cartridge may be used to perform amultiplexed immunoassay with a given sample. The test cartridge containsall of the necessary buffers, reagents, and labels held in sealedchambers integrated into the cartridge to perform the immunoassays.

In another example, a single test cartridge may be used to perform PCR.The DNA and/or RNA may be purified from the rest of a sample (lysate)via a membrane incorporated into the test cartridge. The sample may beextruded through the membrane while a separately stored elution liquidmay remove the DNA and/or RNA and bring it into another chamber to beginthe process of temperature cycling.

Any test such as those described above requires some form of liquidtransport to take place. In an embodiment, the test cartridge includes amoveable, hollow transfer module which includes a plurality of ports toalign to ports along the sides of a cartridge housing. Liquid may betransferred between the other various chambers of the cartridge housingeither into or out of the hollow transfer module by applying a pressuredifferential to the system. In one example, external actuators areutilized to apply the pressure differential.

One of the main limitations of molecular diagnostic instrumentation isthe problem associated with contamination such as cross-contamination,carry-over contamination, etc. Embodiments described hereinsubstantially eliminate by design the contamination of samples to theinstrument.

In one embodiment, the test cartridge offers a self-contained liquidsealed during the manufacturing process. The reagents or the sample donot enter in contact with the environment or with any part of theinstrument. This feature of the test cartridge is also important formany laboratories and hospitals to safely dispose of the products aftertheir use.

Further details relating to the components of the test cartridge systemare described herein with references made to the figures. It should beunderstood that the illustrations of each physical component are notmeant to be limiting and that a person having skill in the relevantart(s) given the description herein would recognize ways to re-arrangeor otherwise alter any of the components without deviating from thescope or spirit of the invention.

First Test Cartridge Embodiment

FIGS. 1-4 illustrate various views and components of a test cartridgesystem according to an embodiment. FIG. 1 illustrates a test cartridgesystem 100 that includes a cartridge housing 102 and a transfer module104. Other components may be considered as well for inclusion in testcartridge system 100, such as an analyzer module or various activecomponents such as pumps or heaters.

Transfer module 104 includes an inner housing 110, a jacket 108, and alid 106. Jacket 108 is designed to fit around inner housing 110,according to an embodiment. In one example, inner housing 110 is made ofa hard material such as metal or plastic, while jacket 108 is made of acompliant material such as rubber or soft plastic. In another example,both jacket 108 and inner housing 110 are made of a soft compliantmaterial, which may be the same material or different materials. Inanother example, both jacket 108 and inner housing 110 are made via anoverinjection process. Lid 106 is designed to seal the end of transfermodule 104 to prevent leakage. Further details regarding the componentsof transfer module 104 are discussed later with reference to FIGS. 3 and4.

Transfer module 104 is designed to be inserted into cartridge housing102 via chamber bay 120. In one embodiment, transfer module 104 isconfigured to connect to an external actuator (not shown). The externalactuator may laterally move transfer module 104 within cartridge housing102 to align ports on transfer module 104 to ports on cartridge housing102. In another embodiment, transfer module 104 is configured to movewithin cartridge housing 102 via operation of an external slider by auser.

Cartridge housing 102 includes a variety of fluidic channels, chambers,and reservoirs. For example, cartridge housing 102 may include aplurality of storage chambers 116 which may contain various buffers orother reagents to be used during an assay or PCR protocol. Storagechambers 116 may be pre-filled with various liquids so that the end userwill not need to fill storage chambers 116 before placing test cartridgesystem 100 into an analyzer. Cartridge housing 102 may further includeone or more processing chambers 124A-C connected to fluidic channelsalong a side of cartridge housing 102. Processing chambers 124A-C may beused for a variety of processing and/or waste applications. In oneexample, chamber 124A is a waste chamber, chamber 124B is an elutionchamber for PCR protocols, and chamber 124C is a swab elution chamber.In an embodiment, cartridge housing 102 includes a grip structure 117 toprovide easier handling of test cartridge system 100.

Samples are introduced into cartridge housing 102 via sample port 114,according to an embodiment. In one example, sample port 114 isdimensioned to completely receive the length of a common medical swab.Thus, the user may place the swab either up to a break-off point orcompletely within sample port 114, and subsequently seal the port with aport lid 112. In another example, sample port 114 receives solid,semi-solid, or liquid samples. In an embodiment, cartridge housing 102includes more than one inlet to introduce samples.

Cartridge housing 102 may incorporate one or more useful structures forperforming tests, such as filters, gels, membranes, etc. For example,cartridge housing 102 may include a membrane housed in cavity 122. Inone embodiment, the membrane is coupled with the fluidic channels alongthe outside of cartridge housing 102. In another embodiment, themembrane may be disposed within any one of processing chambers 124A-C.

The various chambers and channels around cartridge housing 102 may besealed via the use of covers 118, 126, and 128. The covers may be filmscapable of sealing the fluid within cartridge housing 102. In anotherexample, the covers may be plastic sheets or any other means of sealing.In an example, one or more of the covers are transparent.

The integrated test cartridge system 100 allows a user to place a sampleinto, for example, sample port 114, then place test cartridge system 100into an analyzer. In embodiments, the reaction steps to be performedincluding, for example, re-suspension lysing, purification, mixing,heating, binding, labeling and/or detecting can all be performed withintest cartridge system 100 via interaction with the analyzer without anyneed for the end user to intervene. Additionally, since all of theliquids remain sealed within test cartridge system 100, after the testis completed, test cartridge system 100 may be removed from the analyzerand safely disposed of without contamination of the analyzer.

FIGS. 2A-D illustrate various views of cartridge housing 102, accordingto embodiments. The description of each view is set forth to describefeatures that may be present on cartridge housing 102, but should not belimiting as to the placement or dimensional properties of the features.

FIG. 2A provides an example of a side view of cartridge housing 102. Assuch, the view illustrates a plurality of chambers connected by afluidic network and a series of ports which extend into cartridgehousing 102. Each of these groups will be discussed in more detailherein.

The plurality of processing chambers may include a waste chamber 218, anelution chamber 220, and a swab elution chamber 206. Other types ofchambers as would be contemplated by one having skill in the relevantart(s) given the description herein may also be included. Furthermore,the purpose of each chamber may be different than the names specifiedherein.

A plurality of reaction chambers 216 is also shown. Such chambers may beshaped similarly, for example, to a centrifuge tube. In one embodiment,liquid may be drawn into reaction chambers 216 to mix with reagents thathave been pre-loaded into each reaction chamber. For example, eachreaction chamber may be loaded with a different DNA probe, or real timePCR master mix, and liquid may be drawn into each reaction chamber tocreate distinct mixtures in each chamber. The reagents may befreeze-dried before being loaded, or freeze-dried into reaction chambers216. In another embodiment, reaction chambers 216 are also used forsample detection. Thus, in one embodiment, reaction chambers 216 mayalso be considered to be detection chambers. Detection may occur usingan external optical source and photodetector coupled to an analyzer inwhich test cartridge system 100 is placed. Thus, any walls or covers ofreaction chambers 216 may be transparent to allow for optical detection.In one example, the photodetector measures absorbance through the liquidwithin the reaction chamber at one or more wavelengths. In anotherexample, the photodetector measures a fluorescence signal generated froma fluorescent compound within the reaction chamber. In an embodiment,the fluorescence measurements are taken from beneath reaction chambers216. Reaction chambers 216 may be adapted for other means of detection,e.g., electrochemical, electromechanical, surface plasmon resonance,etc.

A set of smaller channel enlargements 214 are observed upstream fromreaction chambers 216, according to an embodiment. Channel enlargements214 may act as liquid sensing areas. As such, channel enlargements 214may be used along with an external optical probe to determine whether ornot liquid is present within channel enlargements 214. Thisdetermination may be used to activate other functions of test cartridgesystem 100. In another embodiment, channel enlargements 214 may includeintegrated sensors, such as a patterned resistive sensor, to indicatethe presence or flow rate of the fluid.

Various fluidic channels connect to each of the chambers or to otherelements within cartridge housing 102. Each channel is also designed toterminate at a port which will interface with the ports or valve regionson transfer module 104. In an embodiment, cartridge housing 102 includestwo main rows of ports such as a row of liquid ports 210, and a row ofvent/suction ports 212. Liquid ports 210 allow fluid to flow to any ofthe chambers depicted in FIG. 2A, or to flow through a filter 222.Liquid ports 210 may act as either inlet ports for liquid to be drawninto transfer module 104 from cartridge housing 102, or as outlet portsfor liquid to be expelled from transfer module 104 to the fluidicnetwork of cartridge housing 102. Vent/suction ports 212 may be used toopen a particular fluidic channel to the atmosphere so that liquid canbe drawn into its corresponding chamber. For example, a vacuum pressuremay be applied to the port illustrated on the far left of the row ofvent/suction ports 212, which would allow for liquid to enter into wastechamber 218 via the second to the left port on the row of liquid ports210. In another example, a vacuum pressure applied from the second tothe left port on the row of vent/suction ports 212 would draw liquidfrom the third to the left liquid port into elution chamber 220. Inanother embodiment, vent/suction ports 212 may be opened to theatmosphere.

Other processing ports 204 can be observed leading into another sectionof cartridge housing 102. Processing ports 204 may lead into or out ofan inner processing chamber. For example, the inner processing chambermay be a bead beater chamber for lysing any cells in the sample. Inanother example, a sample containing solid, semi-solid or liquidmaterial may be placed directly into the inner processing chamber via asecond sample inlet. The material may be homogenized or lysed by theinner processing chamber, and the resultant liquid sample may be drawnfrom the inner processing chamber to transfer module 104 via an innerport (not shown) of the inner processing chamber.

A port may be a small hole extending through the thickness of cartridgehousing 102. In an embodiment, each of liquid ports 210 is designed toalign to another port located on transfer module 104, which can movelaterally between the various liquid ports 210. In an embodiment, eachof vent/suction ports 212 is designed to align to a region aroundtransfer module 104 which allows the port to be either vented toatmosphere or pressurized. The various ports may include a hydrophobicmaterial or have a specific geometry so as to prevent leakage throughthe ports in the absence of any applied pressure.

Filter 222 may be integrated within the fluidic network as illustrated.As such, liquid may pass through filter 222 due to a pressuredifference. Filter 222 may include, for example, a silicate matrix to beused for trapping nucleic acid sequences. In another example, filter 222may be a membrane for extracting plasma from whole blood samples. Otherfilter types may be contemplated as well, such as a reverse-osmosisfilter. In another example, filter 222 may include suitable materialsfor an affinity chromatography column to perform, for example, proteinpurification protocols.

FIG. 2B illustrates another example embodiment of cartridge housing 102.This embodiment includes many of the same features as the examplecartridge housing illustrated in FIG. 2A including waste chamber 218,elution chamber 220, and swab elution chamber 206. However, the fluidicnetwork connected to liquid ports 210 now includes a reaction chamber224, chamber 225 and a plurality of detection chambers 226 a-e. In oneexample, a single fluidic path connects each of reaction chamber 224,chamber 225, and detection chambers 226 a-e together. In anotherexample, the fluidic path terminates at waste chamber 218. A series ofchannel enlargements 214 are illustrated as well and may serve the samepurpose as those in the embodiment described above in FIG. 2A. Thearrangement of chambers described in this embodiment may be useful forimmunoassays or other types of binding affinity assays.

Reaction chamber 224 may contain reagents to be mixed with a samplebefore passing on to detection chambers 226 a-e. The reagents may befirst freeze-dried and placed, or freeze-dried into reaction chamber224, and rehydrated upon contact with the liquid sample. Chamber 225 maycontain a new set of freeze-dried reagents and may be utilized duringPCR protocols to perform further amplification of the nucleic acidsequences. In another example, chamber 225 may contain further reagentsto be mixed with the sample. Alternatively, chamber 225 may contain afilter or capture probes to separate certain compounds from the samplebefore it passes on to detection chambers 226 a-e.

Detection chambers 226 a-e are configured to allow for opticalinterrogation similar to reaction chambers 216 as described above inFIG. 2A. In one example, each detection chamber 226 a-e contains animmobilized probe for performing various binding affinity assays. Atleast one wall of detection chambers 226 a-e is made to be transparentto visible light for fluorescence measurements. In an example, thefluorescence measurements are taken from beneath detection chambers 226a-e.

FIG. 2C illustrates a top view of cartridge housing 102, according to anembodiment. A plurality of storage chambers 230A-E are observed and maybe similar to storage chambers 116 as described previously in FIG. 1. Asample inlet window 232 is also disposed at the top of cartridge housing102, according to an embodiment. Sample inlet window 232 may be used toplace samples into the inner processing chamber. For example, solidsamples may need to be homogenized before testing can begin. These solidsamples may be placed into sample inlet window 232 and enter directlyinto the inner processing chamber.

A row of inlet ports 228 are provided such that each port lies within aunique storage chamber, according to an embodiment. Solution storedwithin the various storage chambers 230A-E may be drawn down through acorresponding inlet port into transfer module 104 at the appropriatetime during a testing procedure. Thus, transfer module 104 also hasanother port located at the top of transfer module 104 which can alignwith each of inlet ports 228. In an example, the lateral movement oftransfer module 104 changes which port of the inlet ports 228 is alignedto the top port of transfer module 104. In another example, inlet ports228 may lead directly to the fluidic network within cartridge housing102 before reaching transfer module 104.

At least one of storage chambers 230A-E may be configured to receive asample that has been placed into cartridge housing 102 via sample port114. For example, storage chamber 230B may be dimensioned so as toreceive a sample cotton swab. In another example, storage chamber 230Bcontains a solution to suspend a sample once the sample has beenintroduced.

FIG. 2D illustrates a view of another side of cartridge housing 102(opposite from the side illustrated in FIG. 2A). Additionally, cartridgehousing 102 includes a pressurized port 236 and a vent port 234,according to an embodiment. Pressurized port 236 may be connected to anexternal pressure source, e.g. a vacuum pump, syringe pump, pressurepump, etc. In one example, the external pressure source is integratedwith the analyzer into which test cartridge system 100 is placed. Thepressure differential applied to the system via pressurized port 236 maybe used to transport liquid throughout the various regions withincartridge housing 102 and transfer module 104. Vent port 234 may beconfigured to open to the atmosphere, according to an embodiment. Assuch, vent/suction ports 212 may lead to a region around transfer module104 that is also coupled to vent port 234. In another example, apressurized source is connected to pressurized port 236 to pull liquidthrough vent/suction ports 212. Any number of ports may be included forthe purpose of pressurizing various regions in and around cartridgehousing 102 and transfer module 104.

In one embodiment, cartridge housing 102 provides structures configuredto center test cartridge system 100 within an automated analyzer. Forexample, a plurality of orifices 235 a-b may be present on cartridgehousing 102 to couple with corresponding pins on the analyzer to aid incentering test cartridge system 100 in regards to an external precisionpositioning system. Oblong protrusions may be used as well to centertest cartridge system 100 within the automated analyzer. At the lowerpart of cartridge housing 102 in FIG. 2D, an optical access area 240 isdisposed below reaction chambers 216, according to an embodiment.Optical access area 240 is configured to be substantially transparent toall wavelengths used during the optical detection process. In oneexample, each individual reaction chamber has its own optical accessarea. In another example, a single optical access area stretches acrossmultiple reaction chambers 216.

A film or plurality of films may be placed over the series of reactionchambers 216. The films may be thin enough to still provide adequatesealing while also allowing for easier heating and/or cooling of thecontents within reaction chambers 216 via an external source. Forexample, the films may be in contact with a surface that is thermallycontrolled by any one of, or a combination of, thermoelectric devices,resistive heaters, and forced air.

FIGS. 3A-D illustrate various views both around and inside inner housing110 of transfer module 104, according to an embodiment. FIG. 3A depictsa perspective view of inner housing 110, according to an embodiment.Inner housing 110 is formed from case 302 which may be a rigid material.For example, case 302 may be a hard plastic or metal material. Inanother example, case 302 may be a flexible plastic material.

Inner housing 110 includes one or more ports which extend through thethickness of case 302. The ports may include a primary inlet port 306and a transfer pressure port 308. In an embodiment, primary inlet port306 aligns with various ones of inlet ports 228 as depicted in FIG. 2C.

In an embodiment, track 304 is used to hold valve jacket 108 in placearound inner housing 110. Valve jacket 108 will be described separatelyin FIGS. 4A-C. Case 302 may also include a coupling region 310 toconnect transfer module 104 to an actuator. The actuator may bemotorized and apply a force upon transfer module 104 to cause movement.In another embodiment, coupling region 310 may be connected to anymanner of structure which allows a user to apply a force to thestructure and consequently move transfer module 104.

FIG. 3B illustrates a side view of inner housing 110. The view shown isthe side which is facing away in FIG. 3A. A similar track 304 isillustrated on this side of inner housing 110 as well. In anotherembodiment, inner housing 110 only includes a single track structure.Also illustrated is a primary outlet port 312. In an embodiment, primaryoutlet port 312 aligns with various ones of liquid ports 210 as depictedin FIG. 2A. It should be appreciated that inner housing 110 may includeany number of ports around the surface of case 302, and theillustrations shown here are not meant to be limiting in their placementand number of ports.

FIG. 3C illustrates a cross-section view of the interior of innerhousing 110, according to an embodiment. Case 302 encloses transferchamber 316. Also included is a chamber cover 318 to seal fluid or anyother sample type within transfer chamber 316.

Primary outlet port 312 is illustrated at or near a lowest point withintransfer chamber 316. The placement allows for any liquids withintransfer chamber 316 to adequately drain through primary outlet port312. To further facilitate adequate drainage, the inner walls oftransfer chamber 316 are sloped downwards, according to an embodiment.In one example, one or more walls of transfer chamber 316 are sloped. Inone example, a wedge 320 is disposed within transfer chamber 316 toprovide a sloped surface.

In an embodiment, transfer chamber 316 contains a stirring element 324.For example, stirring element 324 may be a magnetic stir bar. Stirringelement 324 may be used to effectively mix the contents of transferchamber 316. In one example, stirring element 324 is excited via anexternal magnetic field. In an embodiment, cartridge housing 102includes one or more magnets disposed along the movement path oftransfer module 104. The presence of the magnets may induce a magneticforce upon stirring element 324, causing it to move within transferchamber 316. In another example, stirring element 324 is physicallycoupled to an actuator configured to move stirring element 324.

FIG. 3D illustrates a perspective view of lid 106, according to anembodiment. Lid 106 may include both chamber cover 318 as well as wedge320 coupled to chamber cover 318. The integration of wedge 320 withchamber cover 318 allows for an easier manufacturing process.

Returning to FIG. 3A, the various ports disposed around inner housing110 may be utilized for transferring liquid between various chambers ofcartridge housing 102 and transfer chamber 316. In an example process,transfer module 104 is laterally moved to align primary inlet port 306with one of the plurality of inlet ports 228 of cartridge housing 102.Once aligned, a vacuum pressure may be applied via transfer pressureport 308 which will draw liquid from the storage chamber of cartridgehousing 102 into transfer chamber 316 of transfer module 104. Additionallateral movement of transfer module 104 aligns primary inlet port 306with a different one of the plurality of inlet ports 228 of cartridgehousing 102. A second applied vacuum pressure draws liquid from anotherstorage chamber of cartridge housing 102 into transfer chamber 316. Thetwo liquids within transfer chamber 316 may be further mixed if desiredwith stirring element 324. A third lateral movement of transfer module104 aligns primary outlet port 312 with one of liquid ports 210 ofcartridge housing 102. A positive pressure applied at transfer pressureport 308 expels liquid from transfer chamber 316 through primary outletport 312 and into the fluidic network of cartridge housing 102 via thealigned liquid outlet port. It should be appreciated that many moreliquid drawing and expelling procedures may be performed, and thatliquid may also be drawn into transfer chamber 316 via primary outletport 312.

In order to control fluid flow along particular fluidic channels, aswell as control which regions around the outside of transfer module 104are pressurized, a valve system is implemented around inner housing 110.FIGS. 4A-C illustrate various views of valve jacket 108 disposed aroundinner housing 110.

FIG. 4A illustrates a perspective view of valve jacket 108, according toan embodiment. Valve jacket 108 includes a compliant casing 402 whichfits around inner housing 110. Compliant casing 402 may be a flexiblematerial such as rubber. In an embodiment, the outer surface ofcompliant casing 402 includes ports which extend through the thicknessof compliant casing 402 and align with ports on inner housing 110. Forexample, a first port 410 may align with primary outlet port 312 while asecond port 412 may align with primary inlet port 306.

The outer surface of compliant casing 402 may also include a variety ofpatterned ridges and shapes, according to an embodiment. For example,toroid ridges 404 along a side of valve jacket 108 may be aligned withvarious ones of the plurality of vent/suction ports 212. Additionaltoroid structures 414 are observed along the top of valve jacket 108.Solid toroid structures 414 may align over various ones of the pluralityof inlet ports 228 to protect each port from being unwantedlypressurized. Solid toroid structures 414 are preferred for long termliquid storage in storage chambers 230 a-e. Hollow toroid shapes providethe benefit of reducing friction as transfer module 104 moves withincartridge housing 102.

Other patterned ridges may be present as well. For example, scallopedridges 406 may extend along a length of valve jacket 108 to seal any ofthe plurality of liquid ports 210 which are not aligned with first port410. In another example, straight ridge 408 ensures a homogenouspressure on the inner surface of cartridge housing 102.

The various ridge patterns are designed to press against the inner wallsof cartridge housing 102. This creates a plurality of regions around theouter surface of transfer module 104 which are sealed from one another.Thus, an applied pressure differential in one region will not affect thepressure in the other regions. This example design may be observed moreclearly in FIG. 4B.

FIG. 4B illustrates a cross-section of transfer module 104 withintransfer chamber 102, according to an embodiment. Inner housing 302 andvalve jacket 108 of transfer module 104 are shown, as well asprotrusions 416 off of valve jacket 108. Protrusions 416 may be similarto the ridges and toroid shapes as described previously in reference toFIG. 4A. Protrusions 416 press against the inner walls of cartridgehousing 102 to create a plurality of valve regions, such as regions418A-C, according to an embodiment. For example, region 418B isseparated from regions 418A and 418C due to protrusions 416, and assuch, could be pressurized separately from regions 418A and 418C.

In one example, region 418B is associated with pressurized port 236(FIG. 2D) on a side of cartridge housing 102. An applied pressuredifferential via pressurized port 236 (FIG. 2D) will also pressurizeregion 418B, without pressuring the surrounding regions separated byprotrusions 416.

The cross section view also illustrates how first port 410 of transfermodule 104 may align with one of liquid ports 210 of cartridge housing102. Protrusions 416 may surround port 410 to prevent leakage of fluidor unwanted pressurization of the port region.

FIG. 4C illustrates a side view of valve jacket 108, according to anembodiment. The side view depicted is the side facing away in FIG. 4A.Valve jacket 108 further includes a pressure port 420 which may bealigned with transfer pressure port 308 of inner housing 110, accordingto an embodiment. Pressure port 420 is disposed within a pressurizedregion 424 defined by various ridges, such as straight ridge 428 andserpentine ridge 422. Patterns and/or shapes of the ridges are notlimited to those shown. Another region 426 exists on the other side ofserpentine ridge 422, according to an embodiment. The regions describedin reference to FIG. 4C may be considered similar to the regionsdescribed above with reference to FIG. 4B.

Pressurized region 424 is associated with a port of cartridge housing102, according to an embodiment. For example, when transfer module 104is located within cartridge housing 102, pressurized port 236 may belocated within pressurized region 424. In one example, pressurized portis located below the middle, horizontal portion of serpentine ridge 422.As transfer module 104 translates within cartridge housing 102,pressurized region 424 remains associated with pressurized port 236,according to one example. In another example, translation of transfermodule 104 may align vent port 234 within pressurized region 424 andpressurized port 236 within region 426 due to the serpentine shapeassociated with serpentine ridge 422. A pressure differential appliedvia a port aligned within pressurized region 424 will also apply thesame pressure differential in transfer chamber 316 via pressure port420. In another example, translation of transfer module 104 alignspressurized port 236 with various regions around the outside surface ofvalve jacket 108.

Region 426 is also associated with a port of cartridge housing 102,according to an embodiment. For example, vent port 234 may be locatedwithin region 426, such as just above the middle, horizontal portion ofserpentine ridge 422. In this example, region 426 is opened toatmospheric pressure. Alternatively, pressurized port 236 may be locatedwithin region 426, for example, between a bend of serpentine ridge 422.A vacuum pressure may be applied at pressurized port 236 which similarlypressurizes region 426.

Region 426 may wrap around to the other side of valve jacket 108 (theside depicted in FIG. 4A), according to an embodiment. Thus, the regionsurrounding toroid ridges 404 as well as toroid structures 414 may allbe considered the same region as region 426. In an example embodiment,as transfer module 104 moves within cartridge housing 102 betweendiscrete steps, toroid ridges 404 cover all but one of vent/suctionports 212, according to an embodiment. The one vent/suction port notcovered by toroid ridges 404 is then subjected to either atmosphericpressure or a pressure differential that has been applied to region 426.

Second Test Cartridge Embodiment

FIGS. 5-8 illustrate various views and components of a test cartridgesystem according to another embodiment. FIGS. 5A-5B illustrate views ofa blown out representation for a test cartridge system 500 that includesa cartridge housing 502 and a transfer module 504. Transfer module 504has substantially the same function within the system as transfer module104 from the first test cartridge embodiment. Both transfer modules 504,104 move laterally within the system to line up ports on the exterior ofthe transfer module with ports on the sides of the housing 502, 102,according to some embodiments. Furthermore, transfer module 504 has asimilar construction to transfer module 104 with an inner housing 510surrounded by a jacket 508, and having an internal chamber capped by alid 506. Further details of transfer module 504 are described later withreference to FIGS. 7A-D.

Housing 502 includes many of the same features as housing 102, accordingto some embodiments. For example, housing 502 includes a plurality ofprocessing chambers 524 a-b, a chamber bay 520 for receiving transfermodule 504, and a sample port 514 with a port lid 512. In one example,chamber 524 a is a waste chamber, and chamber 524 b is a swab receptaclechamber. Sample port 514 leads into chamber 524 b, which may bedimensioned to receive the length of a medical swab, according to oneembodiment. Housing 502 also includes various covers 518, 526, 527, and528 for sealing the various chambers and channels around housing 502,according to an embodiment. In one example, each of covers 526 and 518are made from substantially the same material as housing 502. In anembodiment, any one of covers 526, 528, and 518 are substantiallytransparent. Cover 527 may be a material with a high thermalconductivity, e.g., aluminum foil, to allow for more efficient heattransfer to samples within housing 502. An opening 513 may be cut intocover 526 such that heat may be conducted more efficiently from cover527 to an inner processing chamber of housing 502 via opening 513. Theinner processing chamber may also have its own inlet with a cover 532.In an embodiment, housing 502 includes a top opening 522 for receivingvarious types filters to be placed into housing 502. In one example,solid phase extraction materials such as membranes or silica beads maybe placed into a chamber of housing 502 via top opening 522. A pluralityof openings are observed in both covers 526 and 527, according to someembodiments. The openings of cover 526 may align over various smallchambers of housing 502 to, for example, allow more room for dryreagents to be placed into the small chambers. In another example, theopenings of cover 527 may provide optical access to sensing areas of thechannels of housing 502.

Housing 502 also includes an opening 515 into an inner processingchamber, according to an embodiment. Any type of sample, such as solid,semi-solid, or liquid samples, may be placed into the inner processingchamber via opening 515. Opening 515 may be capped by a cover 532 toprevent any leakage from samples placed into the inner processingchamber. Inner processing chamber may be, for example, a bead beaterchamber for lysing cells or homogenizing a sample. Housing 502 may bedimensioned to incorporate various sizes of bead beater modules. In anembodiment, the bead beater modules within housing 502 accept liquidvolumes ranging anywhere from 10 to 5000 microliters. In anotherembodiment, the accepted volumes of the bead beater modules rangebetween 100 and 1000 microliters.

FIGS. 6A and 6B illustrate side views of housing 502 in more detail,according to some embodiments. FIG. 6A illustrates the various storagechambers on a side of housing 502. Housing 502 includes seven storagereservoirs 630 a-g, according to an embodiment. Other numbers of storagereservoirs are also possible. It should also be understood that theillustrated shapes and sizes of the various storage reservoirs 630 a-gare not intended to be limiting and could be altered to includevirtually any shape and size. Each of the various storage reservoirs 630a-g may include two openings into the reservoir. A first opening may becoupled to a fluidic channel to transfer a fluid either into or out ofthe reservoir while a second opening may allow for venting of thereservoir to atmospheric pressure. The ability to vent a reservoir mayallow the reservoir to empty more efficiently when fluid is drawn fromit. Furthermore, air may not be trapped within the reservoir when fluidis moved into it if the air has the ability to escape out of a ventopening.

Also illustrated are two chambers, a first buffer chamber 642 and asecond buffer chamber 643. Each buffer chamber may be used to helpprevent liquid from exiting the fluidic infrastructure of the testcartridge system, according to an embodiment. For example, first bufferchamber 642 may be designed to hold any “spill-over” liquid that hasaccidently flown down a channel used for venting the system. The ventingchannel may also include a liquid sensing area. If liquid crosses theliquid sensing area, a sensor may be designed to shut off any appliedforces that cause fluid to flow in order to stop the liquid before itcan escape out of a venting port. Similarly, second buffer chamber 643may be designed to hold any “spill-over” liquid that has accidentlyflown down a channel used for applying pressure to the system. In someembodiments, the applied pressure is a vacuum pressure for sucking theliquid through various channels and chambers of test cartridge system500. The pressure channel may also include a liquid sensing area with anassociated sensor designed to work in a similar way to the sensordescribed previously in the venting channel. Additionally, each portassociated with first buffer chamber 642 and second buffer chamber 643may include filters 641 a and 641 b, according to some embodiments.Filters 641 a and 641 b may be aerosol filters to prevent contaminationto the rest of the system when using the ports for venting and/orpressurizing the system.

In an embodiment, housing 502 includes clamp points 635 a and 635 b tosupport housing 502 within a larger analyzer system. The test cartridgemay be placed into an analyzer that includes components for heatingand/or cooling the system, optically measuring certain chambers,providing a vacuum or pump source, and actuating the movement oftransfer module 504. Housing 502 of test cartridge system 500 may beheld in place within the analyzer via clamp points 635 a and 635 b sothat housing 502 does not move while the various operations of theanalyzer are being performed.

A waste passage 641 may also be included in housing 502 for guidingfluid and any other waste samples to a waste chamber, such as, forexample, chamber 524 a. The entrance into the waste chamber may bedesigned to only allow fluid to flow into the chamber and not out of thechamber.

FIG. 6B illustrates another example embodiment of the opposite side ofhousing 502. An example fluidic arrangement is presented with aplurality of ports 610 aligned for fluidic coupling with a port oftransfer module 504. Also illustrated are pressure port 636 and ventport 634. Pressure port 636 may be connected to an external pressuresource for applying either positive or negative pressure differentialsthroughout the system, according to an embodiment. Vent port 634 mayeither be open to the atmosphere or connect to another pressure source.For example, a positive pressure difference may be applied to one portwhile a negative pressure difference is applied to the other port toforce a faster movement of liquid through the coupled channels of thesystem.

Housing 502 also includes reaction chambers 616 that may operatesimilarly to reaction chambers 216 described previously in regards toFIG. 2A. In an embodiment, various channels leading to reaction chambers616 include a premixing chamber 631. Premixing chamber 631 may includedry chemicals, such as dried or lyophilized reagents. In anotherexample, premixing chamber 631 includes dry chemistry beads orbiological samples. Such biological or chemical compounds may be storedin premixing chamber 631 for long periods of time before use. Thedimensions of premixing chamber 631 may be designed to specifically fitthe size of a dry chemistry bead, usually on the order of a fewmillimeters in diameter, according to one embodiment. In one example,fluid drawn towards reaction chambers 616 mixes with the samples storedin premixing chamber 631. Various channels also include a sensor region614, according to an embodiment. Sensor region 614 may be used todetermine the presence and/or flow rate of the liquid within thecorresponding channel. An external optical probe may be utilized withsensor region 614 to make the determination. In another example,integrated sensors, such as a resistive sensor, may indicate thepresence or flow rate of the liquid. A control system may use the dataoutput from sensor region 614 to activate various functions of testcartridge system 500, or to control the flow rate of the liquid withinthe respective channel having sensor region 614.

Also illustrated on the side of housing 502 are a plurality of frits633. Each frit 633 may include various materials designed to filter ortrap various particle sizes. In one example, frit 633 is a plasticmaterial having a thin mesh with selectable pore sizes that may rangeanywhere between 0.1 microns to 500 microns. In one embodiment, frit 633has a pore size of around 20 microns.

At the lower part of cartridge housing 502 in FIG. 6B, an optical accessarea 640 is disposed below reaction chambers 616, according to anembodiment. Optical access area 640 is designed to be substantiallytransparent to all wavelengths used during the optical detectionprocess. In one example, each individual reaction chamber has its ownoptical access area. In another example, a single optical access areastretches across multiple reaction chambers 616. In one example, aphotodetector measures absorbance through the liquid within reactionchamber 616 at one or more wavelengths. In another example, thephotodetector measures a fluorescence signal generated from afluorescent compound within reaction chamber 616. The fluorescencemeasurements may be taken from beneath reaction chambers 616 or from theside of reaction chambers 616. Reaction chambers 216 may be adapted forother means of detection, e.g., electrochemical, electromechanical,surface plasmon resonance, etc.

FIGS. 7A-7F provide various views in and around transfer module 504,according to some embodiments. Many of the general features of transfermodule 504 are substantially similar to transfer chamber 104 of thefirst test cartridge embodiment. For example, both transfer modulesinclude a compliant material wrapped around a harder inner housing, andhave ports on the outside that lead inward towards a central chamber.However, the arrangement and design of certain features on transfermodule 504 warrant further discussion, as is provided herein withregards to FIGS. 7A-7F.

Two isometric schematic views from different sides of transfer module504 are illustrated in FIGS. 7A and 7B, according to some embodiments.Transfer module 504 includes jacket 508 wrapped around an inner housing510. Transfer module 504 also includes two ports 712 a and 712 b. In anembodiment, each of ports 712 a and 712 b are disposed on a lowerportion of transfer module 504. In one example, ports 712 a and 712 bare substantially across from one another. Transfer module 504 may alsoinclude a third port 706 along a top portion of transfer module 504. Inan embodiment, ports 712 a, 712 b, and 706 lead into a central chamberinside transfer module 504. Either port 712 a, 712 b, and 706 may beused for coupling to various ports of housing 502 for fluid transfer. Inanother example, either port 712 a, 712 b, and 706 may be coupled to apressurized source for applying a pressure difference to fluid withintest cartridge system 500. In one embodiment, ports 712 a and 712 b areused for transferring fluid only while port 706 is used to pressurize ordepressurize the central chamber of transfer module 504.

Transfer module 504 also includes a variety of patterned ridges andshapes, according to an embodiment. Similar to the patterned structuresof jacket 108 on transfer module 104, the patterned regions on transfermodule 504 may align to various ports of housing 502 and define variouspressurized, or valve, regions around transfer module 504. For example,a toroid structure 704 may align over a port on housing 502 to seal thatport. A cluster of toroid structures 714 is also provided, according toan embodiment. Cluster of toroid structures 714 may be arranged to alignover various ports of housing 502 simultaneously based on a position oftransfer module 504. In one embodiment, a toroid structure from clusterof toroid structures 714 acts as a fluidic bridge between at least twoports of housing 502. In an example, fluid may flow from one channel toanother channel by flowing through two ports that are aligned over thesame toroid structure. In this way, it is possible to move fluid throughdifferent channels of housing 502 without needing to pass the fluidthrough the central chamber of transfer module 504. Fluid may also stillflow into and out of the central chamber of transfer module 504 via anyof ports 712 a, 712 b, and 706, according to an embodiment.

Jacket 508 of transfer module 504 may also include various ridges 707and 709. In an embodiment, ridge 707 is used to seal over various ports610 of housing 502 while only a single port from ports 610 is alignedwith port 712 a. Ridge 709 may be used to differentiate between aplurality of regions, such as, for example, region 711 and 713. In oneembodiment, regions 711 and 713 represent areas that may be pressurizedseparately. For example, region 711 may be pressurized via pressure port636 due to the position of transfer module 504 within housing 502.Pressurizing region 711 may correspondingly pressurize the centralchamber of transfer module 504 via port 706 and draw liquids into, orexpel liquid from, the central chamber of transfer module 504.

Also illustrated on transfer module 504 is a coupling region 702 forconnecting transfer module 504 to an actuator, according to anembodiment. The actuator may be designed to laterally translate transfermodule 504 within housing 502 as substantially similar to the previouslydescribed first test cartridge embodiment.

FIG. 7C illustrates a cross section view of transfer module 504 along alength of transfer module 504, according to an embodiment. Transfermodule 504 includes a central chamber 716. Lid 506 is used to seal theend of central chamber 716. In one embodiment, lid 506 is designed to beremovable. Lid 506 extends into central chamber 716 to provide slopedsurface(s) to help drain any liquids within central chamber 716,according to one embodiment. A hole 708 is disposed substantially in themiddle of lid 506 within central chamber 716 for transferring liquidto/from central chamber 716 from/to other areas of housing 502. Atransfer channel 710 may bring the liquid towards either or both ofports 712 a and 712 b.

FIG. 7D provides a view of lid 506 that includes a panel 718 and asloped structure 720, according to an embodiment. Panel 718 may be usedto seal the end of central chamber 716 while sloped structure 720provides a sloped surface to, for example, facilitate movement of liquidsamples within central chamber 716 towards either port 712 a or 712 b.Hole 708 is also illustrated at a lowest point of sloped structure 720to adequately drain all of the liquid when evacuating central chamber716, according to an embodiment.

FIG. 7E illustrates another view from below lid 506 that shows hole 708and transfer channel 710, according to an embodiment. One exampleincludes side channels 715 to align the liquid with ports 712 a and 712b on the sides of transfer module 504. The illustrated channelconfigurations are just one example for directing fluid into and out ofcentral chamber 716 and should not be considered limiting.

FIG. 7F illustrates a cross section view of transfer module 504 along awidth of transfer module 504, according to an embodiment. Jacket 508 isobserved wrapping around inner housing 510. Jacket 508 includes variousprotrusions 724, according to an embodiment. Protrusions 724 mayrepresent the various patterned structures on jacket 508. In oneexample, protrusions 724 press against the inner walls of housing 502 tocreate various regions 722 a, 722 b, and 722 c. Each region may beseparately pressurized based on a position of transfer module 504 withinhousing 502. Ports 712 a and 712 b are illustrated as being aligned withone of ports 610 of housing 502 and a port associated with pressure port636 respectively, according to an embodiment. As transfer module 504moves laterally within housing 502, ports 712 a and/or 712 b may alignwith different ports 610 of housing 502. Also illustrated within centralchamber 716 is sloped structure 720 and side channel 715, according toan embodiment. In the example embodiment, side channel 715 connects toeach of ports 712 a and 712 b in a U-shape.

FIGS. 8A and 8B illustrate swabs being placed into the test cartridgesystem for analysis, according to some embodiments. FIG. 8A illustratesa swab 802 placed within chamber 524 b of the cartridge housing. Thechamber is sealed with port lid 512. In one example, swab 802 has alength around 80 mm. It should be understood that chamber 524 b may bedimensioned to receive any length of swab without deviating from thescope or spirit of the invention.

FIG. 8B illustrates another embodiment where a longer swab 806 is placedinto chamber 524 b and sealed with an extended lid 804. Extended lid 804may be used to seal over swabs that are longer than chamber 524 b, andstick out from the chamber opening. In one example, longer swab 806 isaround 100 mm in length. Longer swab 806 may be curved and/or bentwithin chamber 524 b.

Exemplary Methods of Operation

Example methods for performing fluid transfer between various chambersof both embodiments of the cartridge housing and its correspondingtransfer chamber are described below.

FIG. 9 displays a flowchart of an example method 900 for transportingliquid through a first embodiment of test cartridge system 100. Itshould be understood that method 900 describes one example operationsequence that can be performed with test cartridge system 100, andshould not be considered limiting. Furthermore, method 900 may also beperformed using the second embodiment of test cartridge system 500.

At block 902, transfer module 104 is laterally moved within cartridgehousing 102 to align an inlet port of transfer module 104 to an outletport of a first chamber, according to an embodiment. The inlet port oftransfer module 104 may be, for example, primary inlet port 306. Theoutlet port of the first chamber may be, for example, any one of the rowof inlet ports 228.

At block 904, a sample is drawn from the first chamber into transferchamber 316 via an applied first pressure differential, according to anembodiment. In an embodiment, the applied pressure differential isapplied at transfer pressure port 308. The applied pressure differentialmay be a vacuum pressure in order to draw the sample into transferchamber 316. The sample may be introduced to the first chamber from acotton swab or a liquid. The first chamber may be, for example, theinner processing chamber or a processing chamber associated with sampleport 114. Additionally, the sample may be any mixture of liquids,semi-solids, solids, etc.

At block 906, transfer module 104 is laterally moved again withincartridge housing 102 to align an outlet port of transfer chamber 316with an inlet port of a second chamber, according to an embodiment. Theoutlet port of transfer chamber 316 may be, for example, primary outletport 312. The inlet port of the second chamber may be, for example, anyone of the row of liquid ports 210. As such, the inlet port of thesecond chamber may lead to any chamber of cartridge housing 102, such aswaste chamber 218, reaction chamber 216, swab elution chamber 206, etc.

At block 908, the sample is drawn from transfer chamber 316 to thesecond chamber via an applied second pressure differential, according toan embodiment. The second pressure differential may be a positivepressure applied at transfer pressure port 308. Alternatively, thesecond pressure differential may be a vacuum pressure applied at avent/suction port 212 to draw liquid into the chamber associated withthe corresponding vent/suction port 212.

It should be understood that many more liquid drawing procedures may beperformed as would be understood by one having skill in the relevantart(s) given the description herein. For example, after block 904, thetransfer chamber may align its inlet port to a second outlet port alongthe top of cartridge housing 102 to draw in another liquid stored inanother storage chamber. This procedure may be repeated as many times asdesired depending on the protocol necessary for the particular moleculartest.

In another embodiment, following block 908, further steps may beperformed to draw the sample back into the transfer chamber, and expelthe liquid into a third chamber. For example, the second chamber may beswab elution chamber 206 while the third chamber may be one of detectionchambers 216. Any number of chambers may have liquid drawn into orextracted out of as many times as desired. Thus, the system allows for amyriad of liquid transfer patterns amongst the various chambers.

FIG. 10 displays a flowchart of an example method 1000 for transportingliquid through a second embodiment of test cartridge system 500. Itshould be understood that method 1000 describes one example operationsequence that can be performed with test cartridge system 500, andshould not be considered limiting.

At block 1002, transfer module 504 is laterally moved within cartridgehousing 502 to align a structure on an outer surface of transfer module504 to at least a first port associated with a first chamber and to asecond port associated with a second chamber, according to anembodiment. The first chamber may be, for example, input reservoir 622while the second chamber may be any of storage reservoirs 630 a-g. Thestructure on the outer surface of transfer module 504 may have a toroidshape to fit around both the first and second ports, according to anembodiment.

At block 1004, a sample is drawn from the first chamber to the secondchamber via at least the structure on the outer surface of transfermodule 504, according to an embodiment. In this way, the sample may movebetween the first and second chamber without passing through, forexample, a central chamber of transfer module 504.

At block 1006, the sample is drawn from the second chamber to a thirdchamber, according to an embodiment. The third chamber may be centralchamber 716 of transfer module 504, and the liquid may enter centralchamber 716 via a port through a wall of transfer module 504. The portmay be, for example, any of fluid ports 706, 712 a or 712 b illustratedin FIGS. 7A and 7B. The third chamber may include components for mixingor filtering the sample. In other embodiments, transfer module 504 maymove laterally to align a port of transfer module 504 to another port ofhousing 502 and expel the sample within its central chamber through thealigned port. It should be understood that many more liquid drawingprocedures may be performed as would be understood by one having skillin the relevant art(s) given the description herein.

EXAMPLES

Two example protocols to be performed using test cartridge system 100are now discussed. The first example protocol is directed to real-timePCR detection, while the second example protocol is directed to animmunoassay. It should be understood that the steps recited here providepossible examples for using the system, as well as for performing eachtest.

PCR Protocol

An example PCR protocol utilizes numerous processing chambers as well asreaction chambers around cartridge housing 102. In one example, the PCRprotocol uses the cartridge housing embodiment illustrated in FIG. 2A.It should be understood that the protocol may also be performed usingthe cartridge housing embodiment illustrated in FIGS. 6A-6B. In thisexample, five storage chambers are used and each contains a pre-loadedsolution. The storage chambers are labeled as such:

R1: Contains a Wash-2 Buffer

R2: Contains a lysis buffer

R3: Contains an elution buffer

R4: Contains a wash-3 buffer

R5: Contains a wash-1 buffer

The example PCR procedure may be carried out using the workflowdescribed herein with reference to example test cartridge system 100described above. Similar steps may be performed using the variouschambers and channels illustrated on test cartridge system 500 as well.The sample is introduced into test cartridge system 100 via a swab intoswab receptacle 114. Alternatively, the sample may be introduced via asecond inlet directly into an inner processing chamber to be lysed by anintegrated bead beater system.

Once the sample has been introduced into test cartridge system 100, theentire test cartridge is placed into an analyzer. The analyzer providesan actuator for moving transfer module 104, one or more heating elementsto perform the PCR reaction, and optical measurement components. Theanalyzer may further couple to the pressure ports around cartridgehousing 102 and apply the necessary pressure differentials.

Transfer module 104 is aligned to draw in lysis buffer from R2 into thetransfer chamber. Transfer module 104 is aligned to move the lysisbuffer to the swab elution chamber 206, where the sample from the swabis re-suspended in the lysis buffer. The sample, along with the lysisbuffer, may then be moved into the inner processing chamber viaprocessing ports 204 to perform lysis on the cells in the sample andrelease the DNA and/or RNA. Following the lysing procedure, the sampleis hereafter referred to as “the lysate.”

The lysate is drawn back into the transfer chamber from the innerprocessing chamber via a vacuum pressure applied at the transferchamber. Then, transfer module 104 is laterally moved to align itsoutput port to a port associated with the waste chamber. However, afilter is disposed upstream from the waste chamber in order to capturethe DNA sequences. Thus, after applying positive pressure to thetransfer chamber, the lysate passes through the filter on its way to thewaste chamber. The DNA will remain within the filter, while the bulk ofany unwanted matter will pass through to the waste chamber. The filtermay be, for example, a silicate matrix or a plurality of silica beadsfor entrapping the nucleic acid sequences.

Transfer module 104 is moved to align with R5 and draw wash-1 bufferinto the transfer chamber. Subsequently, wash-1 buffer is passed throughthe filter to further remove any unwanted material in the filter. Thebuffer passes on to the waste chamber. A second wash step is thenperformed with the wash-2 buffer. Transfer module 104 aligns with R1 todraw in wash-2 buffer and moves again to align back with the fluidicchannel containing the filter. Wash-2 is passed through the filter andon to the waste chamber.

At this stage, it may be required to clean the transfer chamber beforethe DNA can be brought back into it. As such, transfer module 104 isaligned with R4 and the wash-3 buffer is drawn into the transferchamber. The wash buffer may be mixed around in the transfer chamber.Additionally, the wash-3 buffer may be transferred, for example, to theinner processing chamber.

Transfer module 104 is laterally moved to align its top inlet port tothe outlet port of R3. A vacuum pressure is applied to draw the elutionbuffer into the transfer chamber. Afterwards, transfer module 104 islaterally moved to align its outlet port to the port associated withelution chamber 220 on cartridge housing 102. The elution buffer ismoved into elution chamber 220 via an applied positive pressure to thetransfer chamber or via a vacuum pressure from a vent/suction portconnected to elution chamber 220.

The DNA is now ready to be removed from the filter and brought back intothe transfer chamber. The elution buffer from elution chamber 220 ofcartridge housing 102 is drawn through the filter using vacuum pressureback into the transfer chamber that is aligned to the correct port forreceiving the DNA solution. Transfer module 104 may now sequentiallymove between the ports of the various reaction chambers and, via anapplied positive pressure, transfer liquid into each chamber.

Each reaction chamber may contain a reagent necessary for performing PCRwith the DNA. In an embodiment, the reagent is a pre-loaded,freeze-dried pellet which contains any reagents necessary for performingPCR. The reagents will quickly rehydrate when the DNA solution isbrought into each chamber.

Once the DNA solution has been finally transferred into one or more ofthe reaction chambers, the rest of the process may be performed by theanalyzer. That is, cycling of heating and cooling steps in order to atleast one of activate, denature, anneal, and extend the DNA may beperformed. Once the cycling is complete, the optical measurement systemof the analyzer can collect data from each reaction chamber to providetest results to the end user.

Immunoassay

An example immunoassay utilizes at least three of the storage chambersas well as a variety of processing chambers around cartridge housing102. In one example, the immunoassay uses the cartridge housingembodiment illustrated in FIG. 2B. Similar to a PCR protocol, thestorage chambers contain pre-loaded solutions for performing the assay.Additionally, specific capture antibodies may be immobilized within thedetection chambers 226 to provide binding sites to the antigens ofinterest. Fluorescently-labeled antibodies may also be pre-loaded in alyophilized state into reaction chamber 224. In this example, thestorage chambers are labeled as such:

R1: Wash-1 buffer

R2: Assay buffer

R3: Wash-2 buffer

The immunoassay may be carried out using the workflow described hereinwith reference to example test cartridge system 100 for clarity. Thesample may be introduced into cartridge housing 102 through an inletwhich leads directly to an inner processing chamber. Once introduced,test cartridge system 100 is placed into the analyzer. The rest of theprotocol may be performed automatically by the analyzer system. Transfermodule 104 is laterally aligned with the inner processing chamber andthe sample is drawn into the transfer chamber via an applied vacuumpressure.

Once the sample is inside the transfer chamber, transfer module 104laterally moves again to align its output port to a port which leads tothe elution chamber. The sample from the elution chamber is then movedto the transfer chamber by passing through a membrane for obtainingplasma from whole blood. Once the plasma sample (containing the antigenof interest) is back in the transfer chamber, transfer module 104 mayalign with R2 and draw the assay buffer into the transfer chamber. Theassay buffer and the plasma sample are mixed in the transfer chamber.

Once the plasma sample and the assay buffer are mixed, transfer module104 laterally moves again to align its output port to a port which leadsto reaction chamber 224, with the lyophilized fluorescently labeledantibodies. The sample+assay buffer mixture acts to rehydrate thefluorescently labeled antibodies within reaction chamber 224. Therehydrated fluorescent antibodies, the sample plasma, and the assaybuffer are all combined and mixed together. At this stage, if theantigen of interest is present in the mixture, the fluorescently labeledantibodies will have bound to it. In an embodiment, heating and/ormixing may be performed to enhance the reaction.

The resultant mixture is transported from reaction chamber 224 to eachof detection chambers 226. Once again, the mixture may be gently mixedor heated in each detection chamber 226 to ensure interaction betweenthe immobilized capture antibodies and the antigen within the mixture.

Once mixing is complete, transfer module 104 aligns with R1 and drawsthe wash-1 buffer into the transfer chamber. The wash-1 buffer may befirst transferred into the reaction chamber and subsequently into eachdetection chamber containing the mixture. The wash-1 buffer clears awayany unbound material. The wash-1 buffer continues through the detectionchambers and passes into the waste chamber.

A second wash step may be performed. Transfer module 104 aligns with R3and draws the wash-2 buffer into the transfer chamber. The wash-2 buffermay be first transferred into the reaction chamber and subsequently intoeach detection chamber containing the mixture. The wash-2 buffer clearsaway any unbound material. The wash-2 buffer continues through thedetection chambers and passes into the waste chamber. At this stage, anybound material to the immobilized antibodies should be the antigen ofinterest along with the bound, fluorescently labeled antibody.

The optical measurement system of the analyzer can now be used for eachdetection chamber to quantify the amount of antigen based on thereceived fluorescent signal. The data collected may, for example, beplotted against a standard curve performed previously with calibratorsto obtain the quantitative results for the end user.

It should be appreciated that at the end of either protocol discussedabove, the entire test cartridge system 100 may be removed from theanalyzer and safely disposed of. In another embodiment, the resultantsolution within one or more of the detection chambers may be extractedfor further analysis. Since the system is self-contained, numerous testcartridges may be used with the same analyzer without concern forcross-contamination or fouling between experiments.

It is to be appreciated that the Detailed Description section, and notthe Summary and Abstract sections, is intended to be used to interpretthe claims. The Summary and Abstract sections may set forth one or morebut not all exemplary embodiments of the present invention ascontemplated by the inventor(s), and thus, are not intended to limit thepresent invention and the appended claims in any way.

Embodiments of the present invention have been described above with theaid of functional building blocks illustrating the implementation ofspecified functions and relationships thereof. The boundaries of thesefunctional building blocks have been arbitrarily defined herein for theconvenience of the description. Alternate boundaries can be defined solong as the specified functions and relationships thereof areappropriately performed.

The foregoing description of the specific embodiments will so fullyreveal the general nature of the invention that others can, by applyingknowledge within the skill of the art, readily modify and/or adapt forvarious applications such specific embodiments, without undueexperimentation, without departing from the general concept of thepresent invention. Therefore, such adaptations and modifications areintended to be within the meaning and range of equivalents of thedisclosed embodiments, based on the teaching and guidance presentedherein. It is to be understood that the phraseology or terminologyherein is for the purpose of description and not of limitation, suchthat the terminology or phraseology of the present specification is tobe interpreted by the skilled artisan in light of the teachings andguidance.

The breadth and scope of the present invention should not be limited byany of the above-described exemplary embodiments, but should be definedonly in accordance with the following claims and their equivalents.

What is claimed is:
 1. A method comprising: laterally translating atransfer module within a housing to align a structure on an outersurface of the transfer module with a first port associated with a firstchamber and with a second port associated with a second chamber; drawinga sample from the first chamber to the second chamber via at least thestructure aligned over the first port and the second port; and drawingthe sample from the second chamber to a third chamber located within thetransfer module via a port through a wall of the transfer module.
 2. Themethod of claim 1, further comprising mixing the sample introduced intothe first chamber with a buffer disposed within the first chamber. 3.The method of claim 1, further comprising mixing the sample drawn intothe third chamber with a liquid already present in the third chamber. 4.The method of claim 1, further comprising: introducing the sample to thefirst chamber via a swab carrying the sample.
 5. The method of claim 1,further comprising: laterally translating the transfer module to alignthe port of the transfer module to a port of a fourth chamber; drawingthe sample into the fourth chamber from the third chamber; and measuringone or more qualities of the sample while in the fourth chamber.
 6. Themethod of claim 5, wherein measuring comprises optically measuring afluorescence signal.
 7. The method of claim 5, wherein measuringcomprises optically measuring an absorbance.
 8. The method of claim 5,further comprising heating the sample after either drawing the sampleinto the third chamber or drawing the sample into the fourth chamber. 9.The method of claim 5, wherein drawing the sample into the fourthchamber comprises flowing the sample through a filter.
 10. The method ofclaim 5, wherein drawing the sample into the fourth chamber comprisesflowing the sample through a fluid splitter into one or moresub-chambers.
 11. The method of claim 1, further comprising repeatinglaterally translating the transfer module to align the port of thetransfer module with various ports of one or more chambers.
 12. Themethod of claim 9, further comprising drawing one or more liquids intothe third chamber from the one or more chambers via one or more pressuredifferentials.
 13. The method of claim 1, further comprising mixing thesample within the third chamber with a magnetic stir bar.